Field of the Invention
The present invention relates to reprogrammed cells and stem-like cells of hepatic origin, and methods of making and using the same.
Description of Related Art
Some hepatoma cell lines have been extensively used such as HepG2, HuH7, etc. Such cells have drawbacks, including the lack of availability of a cell bank, and a progressive loss of many hepatic functions. HepaRG® cells (human hepatoma cell line deposit no. 1-2652, filed on 5 Apr. 2001 at the Collection Nationale de Cultures de Microorganismes, Institut Pasteur, 25 rue du Docteur Roux, F-75724 Paris Cedex 15, U.S. Pat. No. 7,456,018, incorporated by reference herein) are terminally differentiated hepatic cells derived from a human hepatic progenitor cell line that retains many characteristics of primary human hepatocytes. Cryopreserved and differentiated HEPARG® cells (Biopredic, Inc.) are now widely used for many cell-based applications. Up to now, this line has been the best hepatic cell line in its ability to morphologically and functionally mimic primary human hepatocytes in vitro.
One crucial advantage of HEPARG® is the established cell bank, making possible long term high level of functional stability by regularly restarting new batches of cells from the original pool of cells. However, HEPARG® has 3 main limitations: 1) The cell bank has some limitations in number of frozen vials, 2) Although the cells have high reproducibility for 17 passages, the stability of the line is limited to 17-18 passages, which represents a strong limitation for long term experiments (requiring delivery to customers at passage 12 for preserving the bank); and 3) The limited plasticity of the cells thus limiting diversification of properties and as consequence, also limiting new applications. There remains a need for hepatic cell lines with functions mimicking primary human hepatocytes.